DESCRIPTION: The biological effects of low-energy electromagnetic fields (EMFs) is controversial with no consensus of the fundamental principles potentially involved. Although several sites of interaction at the cellular level, such as ion channels, gap junctions, and molecular components of signal transduction pathways, have been suggested as likely targets for modulation by EMFs, there is little direct evidence. Recent results from in vivo and in vitro studies suggest that power frequency EMFs may exert co-promoting activity with the chemical tumor- promoter 12-O-tetra-decanoylphorbol-13- acetate (TPA.) A 60-Hz exposure system is being used to study the mechanism by which EMFs may potentially act to promote cancer. Preliminary studies were designed to evaluate the hypothesis that power frequency EMFs may amplify the signal transduction pathway induced by TPA. Their approach is to use in vitro cell culture models demonstrating reproducible biological effects of EMFs to study the cellular mechanisms involved. Because it is unlikely that any single in vitro model system will be convincing on its own and multiple mechanisms may be involved in mediating EMF effects, their approach is to use increasingly more specific endpoints.The tumor-promoter-responsive JB6 cell line will be used to determine the EMF conditions required for demonstrating co- promotion of colony formation by TPA and epidermal growth factor (EGF.) The effect of EMF and TPA on homologous and heterologous gap junctional communication will be evaluated by using a flow cytometric dye-transfer assay. Further, a model system to investigate the effect of EMFs on the activation of NF-kappaB and in mediating the activation of gene expression has been devised to further explore the relationship between calcium, reactive oxygen intermediates (ROIs), NF-kappaB DNA-binding, HIV1-LTR activity, and the response to EMFs. Thus, these studies will evaluate the hypothesis that EMFs may amplify signal transduction by having an effect on reactive oxygen intermediates produced as a consequence of signal transduction.